Tens of millions of Americans suffer from chronic pain. This long-lasting pain is caused by a series of events along nerve cell membranes that make neurons hypersensitive. Injecting excess PAP into the system triggers a parallel series of reactions that makes it harder for this pain cascade to fire.

“Essentially PAP robs the cell of PIP2 so pro-pain pathways can’t signal as effectively,” explained Zylka. The team conducted their research using cell cultures and mice.

Using PAP to deplete PIP2 represents a promising new approach to treating chronic pain. “This is something people haven’t really focused on yet,” Zylka said. “We’re going right to the source of these pathways.”

In previous studies using mice, the team found that injecting PAP after an injury reduces sensitivity to both heat (like touching a hot burner) and mechanical sensitization (like the pain from brushing sunburned skin) for three days.

This time, the researchers took it a step further by injecting PAP before the injury. The effects lasted for the duration of the study—up to nine days.

Patients undergoing major surgery occasionally receive pain relievers through spinal injections just before the surgery begins. This study suggests that injecting PAP along with those other pain relievers might reduce patients’ need for analgesics like opiates in the days following surgery. Future studies with patients will be needed to verify these possibilities.

“Ultimately, we’re very interested in other pain-related mechanisms that regulate PIP2 levels in cells. Any one of those mechanisms could be targeted for the treatment of chronic pain,” Zylka said. Such research could provide new drugs for patients who already have chronic pain.

Study co-authors include UNC graduate student Nathaniel Sowa, UNC postdoctoral fellow Sarah Street, and Pirkko Vihko, professor and chief physician at the University of Helsinki, Finland, who generated the PAP knockout mouse model that was used in this study.

The research was undertaken at UNC and was supported by grants from the Sloan Foundation, the Searle Scholars Program, the Klingenstein Foundation, the Whitehall Foundation, the Rita Allen Foundation and the National Institute of Neurological Disorders and Stroke, a component of the National Institutes of Health.